Continuous infusion of cefazolin is superior to intermittent dosing in decreasing infection after hemorrhagic shock

Standard doses of antibiotic administered by intermittent infusions after hemorrhagic shock have decreased efficacy in combating infection. This study compared identical quantities of cefazolin administered after shock as intermittent doses or as continuous infusions in a subcutaneous abscess model. One hour after resuscitation from shock, rats were inoculated with 2 x 10(8) Staphylococcus aureus subcutaneously on the dorsum and divided into three groups: (1) control rats, which received no drug treatment; (2) rats in the intermittent group, which received cefazolin at either 30 or 60 mg/kg intraperitoneally, 30 minutes prior to inoculation, then every 8 hours for three doses, and (3) rats in the continuous infusion group, which received cefazolin at either 30 or 60 mg/kg intraperitoneally, 30 minutes prior to inoculation, followed by cefazolin, 90 or 180 mg/kg, intraperitoneally by continuous infusion more than 24 hours after inoculation. Seven days after the inoculation, abscess number, diameter, and weight were measured. Rats that received either dosage of cefazolin intermittently had the same abscess rate after shock as control rats. Rats that received a continuous infusion of cefazolin at either dose had 56% fewer abscesses than control rats. Abscess diameter and weight decreased with increasing quantities of cefazolin, and abscesses were always smaller in rats receiving the continuous infusion. There were no differences in peak subcutaneous cefazolin levels between the intermittent and continuous groups. Continuous infusion provided significantly more cefazolin to the tissue than an equivalent quantity of cefazolin delivered as intermittent doses. These data demonstrate that continuous infusion of cefazolin provided more antibiotic to the tissue and was superior to intermittent injection in reducing infection after hemorrhagic shock.